Increased demands on amphetamine dependence treatment services point to a need for effective pharmacotherapies for withdrawal symptom suppression. However, empirical data on which to base effective treatments are scarce. To address the need for an evidence base, four studies were conducted in two countries - Australia and Thailand. Firstly, the time course and severity of amphetamine withdrawal symptoms were characterised in two inpatient samples of amphetamine users. Results identified the first week of abstinence as an acute withdrawal phase characterised by increased sleeping, eating and a cluster of mood and anxiety - related symptoms. Following the acute phase, most withdrawal symptoms remained stable and at low levels for the remaining two weeks of abstinence ( the sub - acute phase ). Data from these two studies formed the basis for a new instrument, the Amphetamine Cessation Symptom Assessment scale ( ACSA ). On psychometric testing, the ACSA showed satisfactory reliability and a clear psychometric structure, delineating symptom clusters and their correlates with a three factor solution providing the best fit to the data. Using the ACSA to measure outcome, the safety and efficacy of the serotonin and noradrenaline reuptake inhibitor antidepressant mirtazapine ( 15 - 60 mg per day, n = 13 ), and the wake-promoting drug, modafinil ( 400mg per day, n = 14 ) were assessed in successive, open - label, inpatient pilot trials. Study medication was administered for up to ten days. An historical comparison group ( n = 22 ) who received treatment as usual consisting of pericyazine 2.5 - 10mg per day for control of agitation served as a comparison. Results showed that modafinil and mirtazapine were well tolerated, producing minimal positive subjective effects. There were significant group differences in withdrawal severity ( F = 18.6, df 2,219 p < 0.001 ). Post - hoc analysis showed that modafinil was more effective than mirtazapine ( p = 0.041 ), and both were more effective than treatment as usual ( both p < 0.001 ) in ameliorating withdrawal severity. Overall, these studies identified a peak in withdrawal severity during the first week of abstinence ; demonstrated the reliability and validity of the ACSA and identified modafinil as a safe and potentially effective pharmacotherapy for the treatment of amphetamine withdrawal symptoms. / Thesis (Ph.D.)--Medical School, 2005.

<p>Porphyrias are inherited metabolic disorders characterised by an impairment of heme biosynthesis. Acute intermittent porphyria (AIP) is the most common of the acute porphyrias in Sweden. Acute attacks of AIP are characterised by neuro-psychiatric symptoms, including epileptic seizures. Environmental and acquired factors are related to the induction of symptoms. Acute attacks of AIP are treated with high doses of glucose and/or hematin infusions.</p><p>The pathogenesis of the neuro-psychiatric symptoms is not known. Reversible white-matter lesions, probably due to vasospasm, have been seen on brain MRI. Similarities between multiple sclerosis (MS) and AIP have previously been described, but to our knowledge no study has investigated whether AIP-gene carriers have white-matter lesions seen on brain MRI or oligoclonal bands (OB) in cerebrospinal fluid (CSF).</p><p>The percentage of AIP-gene carriers who have experienced epileptic seizures has been calculated at 10-20%, but previous investigations are derived from highly selected clinic-based studies. Studies were therefore undertaken to investigate the prevalence of epileptic seizures, the relationship of seizures to AIP, the type of seizures and the relationship of seizures to other factors such as melatonin.</p><p>A case report described the disappearance of porphyric attacks after the onset of diabetes mellitus (DM). In our study, we investigated the rate of attacks after the onset of DM. For many years, clinical issues relating to AIP have not been a focal area. We therefore carried out a study to update our knowledge of the clinical course of AIP in order to improve prevention, control and treatment. In our studies of AIP-gene carriers and epileptic seizures, we found that epileptic seizures are less common than has previously been described (3.7%) and they are not very different from what is expected in the general population, but the prevalence of 5.1% of seizures with manifest AIP is higher than in the general population. The seizures may be generalised or partial and the seizure frequency was generally low. The AIP-gene carriers who had had epileptic seizures had a lower melatonin excretion level in their urine compared with gender- and aged-matched AIP-gene carriers’ relatives without epileptic seizures, which may indicate that melatonin plays a possible anti-convulsive role.</p><p>In our study of AIP and DM, no subject had an attack of AIP after the onset of DM. White-matter lesions on brain MRI were seen in 25% of the AIP-gene carriers examined outside attacks. One carrier had elevated protein levels in the CSF, but no carrier had cells or OB in the CSF.</p><p>In our population-based study, 356 DNA-confirmed AIP-gene carriers from northern Sweden participated. Manifest AIP (MAIP) was identified in 42%, 65% of whom were women. Eight mutations were found. Women were more severely stricken by AIP attacks in terms of number and duration, hospital admission and early onset. Men (30%) reported most attacks > 40 years of age. The most commonly reported symptoms during attacks were severe abdominal pain (86%), fatigue (42%), constipation (41%), vomiting (36%), muscle pain (30%), psychiatric symptoms (29%), pareses (20%) and sensory impairment (10%). Chronic AIP symptoms were reported by 18%. Precipitating factors were often reported: menstruation (31%), psychological strain (30%), certain drugs and fasting (20%), infection and alcohol (14%), physical strain (12%) and pregnancy (5%). Smoking was more frequent in MAIP and was associated with the number of AIP attacks. Some 30% of MAIP carriers used drugs that were not considered safe (in 1999), mainly diuretics, calcium antagonists and ACE inhibitors. Twenty per cent of MAIP carriers reported that they were receiving a disability pension due to AIP. Elevated levels of ASAT, bile acids, creatinine, creatinine clearance, U-ALA and U-PBG were often found in MAIP-gene carriers. Hypertension, renal impairment and pain in the legs were associated with MAIP. Hepatoma was strikingly over-represented.To summarise; epileptic seizures are less common than has previously been described, melatonin may have an anti-convulsive effect and DM may have a beneficial effect on MAIP-gene carriers. White-matter lesions are seen on brain MRI. The lesions are unspecific but may relate to the patients’ porphyria. AIP is not a harmless disease. A large percentage of the AIP-gene carriers had frequent attacks, severe symptoms, long-lasting fatigue and chronic AIP and women were more severely stricken. Effects on the kidneys, blood pressure and the liver, including HCC, were evident. Measures should be taken to improve the quality of life and prognosis for AIP-gene carriers.</p>

<p><strong>Sammanfattning</strong></p><p>Syftet med denna litteraturstudie var att undersöka och beskriva hur hjärtinfarktsymtom yttrar sig och upplevs av kvinnor och vilka atypiska symtom sjuksköterskan bör vara uppmärksam på i mötet med kvinnor i sjukvården. En beskrivande litteraturstudie genomfördes där vetenskapliga artiklar av kvalitativ och kvantitativ karaktär analyserades. Huvudresultatet visade att central bröstsmärta var ett vanligt rapporterat symtom men att många kvinnor inte hade bröstsmärta som det enda och huvudsakliga symtomet. Kvinnor tenderade mer ofta än män att uppleva besvär från käke, hals och nacke. Rygg och skulderbladsmärta visade sig förekomma i liknande utsträckning som bröstsmärta hos kvinnor med hjärtinfarkt. Extrem trötthet tillsammans med dyspné var två av de mest frekvent rapporterade <em>tidiga</em> teckenen vid hjärtinfarkt, dessa upplevdes ofta lång tid innan hjärtinfarkten men var för kvinnorna svåra att sammankoppla med hjärtinfarkt. Illamående och kräkning var frekvent rapporterande symtom som framför allt visade sig i den akuta fasen av hjärtinfarkt. Svettningar i kombination med andra symtom var också vanligt i den akuta fasen av hjärtinfarkten, kraftig svettning var något som fick kvinnor att reagera på att något var allvarligt fel och det påverkade kvinnors beslut att söka sjukvård.</p> / <p><strong>Abstract</strong></p><p>The aim of this literature study was to explore and describe how the heart attack symptoms manifested and were experienced by women and the atypical symptoms the nurse should be alert to when meeting women in health care. A descriptive literature review was conducted in which scientific papers of qualitative and quantitative characteristics were analyzed. The main results showed that central chest pain was a commonly reported symptom, but that many women did not have it as the only and main symptom. Women tended more often than men to experience symptoms of jaw, neck and throat. Back and shoulder pain were found to occur in a similar extent as chest pain in women with myocardial infarction. Extreme fatigue with dyspnoea' were two frequently reported early signs of heart attack, often felt long before the heart attack but difficult for women to connect with myocardial infarction. Nausea and vomiting were symptoms that mainly appeared in the acute phase of myocardial infarction. Sweating in combination with other symptoms were also common in the acute phase of myocardial infarction, excessive sweating was something that got women to respond to that something was seriously wrong and it affected women's decisions to seek care.</p><p> </p><p> </p>

<p>One hundred haemorrhoid patients were compared with 300 matched control persons. Haemorrhoid symptoms and bowel symptoms were studied. Most common symptom of the patients was bleeding (44%), followed by prolapse (24%), hygiene problem (14%), pain (12%) and itching (5%). Bowel symptoms, as bloating and evacuation difficulties, possibly related to IBS, were frequent among the patients.</p><p>556 patients were operated upon with Milligan-Morgan haemorrhoidectomy. 418 (81%) answered a questionnaire on results, and on disturbances in anal continence. Totally140 (33%) reported recurrence, and 139 (33%) patients reported anal incontinence. Forty of the 139 patients associated this to the surgical procedure. Female gender was associated to increased risk of incontinence.</p><p>The 40 patients who reported incontinence, were invited to undergo ano-rectal manometry, saline infusion test, endo-anal ultrasound, proctoscopy and clinical examination. Altogether 19 patients approved to participate. Matched control subjects and 15 persons previously operated for haemorrhoids, but without symptoms of incontinence, served as two reference groups. Incontinence score and saline infusion test showed significantly poorer continence in the patient group. Endo-anal ultrasound showed injury to the external sphincter in 20% of the patients. Anal pressure was slightly lower in the patient group, but the difference was not significant. </p><p>Totally 225 patients were randomised to Milligan-Morgan or Ferguson haemorrhoidectomy. Primary aim was to study changes in anal continence. Other aims were to study postoperative pain, wound healing, complications, patient satisfaction and recurrence and changes in bowel function. Patients in the Ferguson group reported, slightly quicker wound healing (P=0.06). Postoperative pain was equal, as was rate of complications. After one year the Ferguson group reported lower incontinence score, and more satisfied patients. Recurrence rate was equal, 15-17%. Most bowel symptoms were reduced one year after surgery.</p><p>In conclusion, functional bowel symptoms are common in haemorrhoid patients. Haemorrhoidectomy is associated with risk for incontinence in 5-10% of patients and females are at greater risk. A proportion of the patients who claim postoperative incontinence have physiological signs of sphincter incompetence, and external sphincter injuries are observed in those patients. Ferguson haemorrhoidectomy results in better anal continence and more satisfied patients. </p>

<p>Elderly committing suicide can be in a “preclinical phase” of dementia. Depressive symptoms may indicate a risk to develop a disease of dementia, for example Alzheimer’s Disease. Today almost 10% of the Swedish population older than 65 years suffer from a cognitive impairment diagnosed as dementia. Symptoms of dementia are associated with degenerative changes in the brain caused by a deposition of amyloid, leading among others things to a nerve cell death. A clinical diagnosis can be hard to set, and a definitive diagnose can only be set after a pathological examination, which only is possible after death. For this study we used Congo red staining of brains sections to find amyloid in autopsies from elderly people committing suicide. 35 cases (>60 year) were studied. Of the 35 cases 1/3 showed to be positive for amyloid deposition. This result in addition to other studies suggest that depressive symptoms is a “preclinical phase” of dementia, and therefore the suicide risk for this group must be consider to be elevated. However, more reliable prospective studies most be done to confirm this retrospective study.</p>

The purpose of this retrospective study was to examine the predictive value of quantitative MRI disc displacement for changes of TMD signs and symptoms in a pre-orthodontic adolescent patient sample. The sample consisted of fifty-five adolescent patients who had baseline temporomandibular joint MRI and longitudinal clinical records of TMD signs and symptoms. Thirty-eight were females and seventeen were males. The mean age was 12.9 ±1.6 years (range 7.4-16.6). Our analysis revealed that MRI right disc displacement has significant association with changes of ipsilateral joint locking. However, predictive value of disc displacement for changes of joint locking could not be analyzed due to small sample size. Nevertheless, MRI right disc displacement can distinguish subjects with persistent ipsilateral clicking from those who were persistently free of clicking from T1 to T2. These findings indicate that clinical assessment of right joint clicking is consistent with MRI determination of disc displacement.

The overall aim of this thesis was to elucidate and investigate psychophysiological aspects and effects of acupuncture and needle stimulation. Within this framework emphasis was directed toward the effects of needle stimulation (acupuncture) on muscle blood flow in the tibialis anterior and trapezius muscles in healthy subjects and patients suffering from chronic muscle pain. This study also included evaluation of a new application of photoplethysmography in noninvasive monitoring of muscle blood flow. The evaluation was based on experiments known to provocate skin or muscle blood flow. The psychological aspects studied comprised the effects of manual acupuncture on pain in fibromyalgia patients and the effects of electro-acupuncture on psychological distress and vasomotor symptoms in postmenopausal women in the clinical context. The results showed that photoplethysmography have potential to noninvasively monitor muscle blood flow and to discriminate between blood flow in skin and muscle, although some considerations still have to be accounted for. It was further shown that muscle blood flow change in response to needle stimulation differed between healthy subjects and patients. Deep needle stimulation in the muscle of healthy subjects consistently increased muscle blood flow more than subcutaneous needle stimulation. In the painful trapezius muscle of FMS patients, however, subcutaneous needling was equal or even more effective in increasing muscle blood flow than deep intramuscular stimulation. Generally, needle stimuli had weak effect on blood flow in the trapezius muscle of the severely affected trapezius myalgia patients, possibly depending on older age and lesser number of patients included in the study. The different patterns of blood flow response to needle stimulation between healthy subjects and patients with chronic muscle pain might be a manifestation of altered somatosensory processing in the patients. The clinical studies showed that best pain relief of acupuncture in FMS patients was achieved in the neck-shoulder region, while the effect on the generalised symptoms was of short duration. Well-being and sleep was found to best predict treatment outcome. The results suggest that acupuncture treatment may be used for the alleviation of neck-shoulder pain, primarily, but it is not an alternative as the sole treatment. Electro-acupuncture, significantly decreased psychological distress and climacteric symptoms in postmenopausal women, but not better than a (near-) placebo control, implying pronounced non-specific effects. / Akupunktur ingår som en del i traditionell kinesisk medicin (TCM) och har använts i över 2000 år för att lindra sjukdom och symptom. I Sverige blev akupunktur godkänd som smärtlindringsmetod inom Hälso- och Sjukvården 1984. Sedan nästan 10 år är akupunktur jämställd med övrig behandling i sjukvården vilket innebär, att akupunktur kan användas även för behandling av annat än smärta. Förutsättningen är emellertid, att det finns tillräckligt med vetenskapliga belägg, s.k. evidens, för detta. I de allra flesta fall saknas det idag. För att säkerställa att evidens föreligger krävs omfattande forskning om effekter av akupunktur. Syftet med de olika studierna i avhandlingen var att belysa och studera psykologiska och fysiologiska aspekter och effekter av akupunktur och nålstimulering. Effekt på blodflöde i hud och muskel undersöktes på friska personer och på patienter med kronisk muskelsmärta. Normalt krävs ett mindre kirurgiskt ingrepp för att mäta blodflöde i muskel, men i dessa studier användes en mätmetod, som enkelt och utan ingrepp (icke-invasivt) i normala fall används för att mäta blodflöde i huden, s.k. fotopletysmografi (PPG, eng.). Med hjälp av ny teknik användes PPG i dessa studier för att mäta även muskelblodflöde. En studie för utvärdering av den nya PPG-tekniken ingick också i avhandlingen. Utvärderingen av mätmetoden visade goda möjligheter att mäta muskelblodflöde icke-invasivt med hjälp av PPG. Hos friska personer blev effekten på blodflödet störst vid djup stimulering i muskeln och där den s.k. DeQi-känslan framkallades (som vid klassisk akupunktur). Hos patienter med fibromyalgi var nålstimulering i huden lika, eller t.o.m. mer, effektiv att öka muskelblodflödet i skuldran än den djupa nålstimuleringen. De olika mönstren av blodflödesökning mellan de friska personerna och patienterna kan bero på ett förändrat reaktionssätt i nervsystemet som svar på smärtsam stimulering. I två kliniska studier studerades den smärtlindrande effekten av manuell akupunktur vid fibromyalgi och effekten av elektroakupunktur på stress och klimakteriebesvär hos kvinnor i övergångsåldern. Akupunktur vid fibromyalgi visade sig ha bäst smärtlindrande effekt i nack-skulderområdet, medan effekten på de generella symptomen var kortvarig. Patienter som mådde och sov relativt bra erhöll bäst effekt. Efter en behandlingsserie, bestående av elektroakupunktur, minskade stress och klimakteriebesvär påtagligt hos kvinnorna i övergångsåldern, men inte mer än hos en grupp kvinnor, som fick en kontrollbehandling bestående av mycket ytligt placerade nålar i huden. Detta tyder på att en betydlig del av behandlingsresultatet utgjordes av ospecifika effekter eller, s.k. eller placeboeffekter.

Coeliac disease (CD) is considered to be the result of a complex interplay of intrinsic (genetic) factors and variable extrinsic (environmental) factors. The complex background of CD explains its wide spectrum of clinical manifestations. For a very long time CD was considered more or less a disease of childhood, which was extremely rare in adults. Nowadays we know that CD is one of the most common food intolerance disorders. An epidemiological study of CD in a geographically defined area of Sweden (Paper1) showed a prevalence of 95.5/ 100 000 inhabitants. Among the associated diseases an especially high incidence of associated thyroid disease, 10.8% was observed. In a fifteen-year cohort follow up study of all CD-patients residing in the counties of Örebro and Linköping (Paper 2) the total mortality was increased with 38% (SMR 1.38 95% C.I. 0.31-0.83). This was mainly explained by a 48% increased death rate in ischemic heart disease, significant in patients over 65 years (SMR 1.58 95% C.I. 1.00-2.06). However, there was a 47 % lower risk of all malignancies (SIR 0.53 95% C.I. 0.31-0.83). A cohort of 22 consecutively biopsy-proven adult CD patients (Paper 3), were followed in respect of antibody titres from diagnosis and after 1, 3, 6, and 12 months on a gluten free diet (GFD). All antibody titres fell sharply within one month. Thus excluding a CD diagnosis serologically on a patient who has initiated a GFD by herself is not to recommend. In another cohort with CD patients (Paper IV) who were diagnosed 8-12 years earlier recommended and who were recommended, the reliability of diet history, serological and biochemical markers to predict the appearance of the small intestinal mucosa were analysed (Paper IV). The history of a strict GFD gave a predictive value of 88% of a mucosa in remission. The values of serological tests (AGA, EmA and tTG) to predict a mucosa in remission were 93% for all. In CD patients in remission gastro-intestinal symptoms were evaluated with the GSRS questionnaire. Subjects with CD reported significantly more GI-symptoms than a general population sample (p&lt;0.01). This was particularly true for women with CD who scored worse than female controls .By contrast men with CD reported no more symptoms than male controls.

This thesis aims to describe the initial phase of an acute coronary syndrome (ACS) in overall terms from a national perspective and to evaluate the impact of an information campaign designed to inform the public about how to act when suspecting an ACS. A total of 1939 patients at 11 hospitals in Swedenwith diagnosed ACS and symptom onset outside hospital completed a questionnaire(I-IV).In Study V, a questionnaire was completed by 116 patients withACS before the campaign and 122 after it. Register data were followed every year to evaluate ambulance use and emergency department (ED) visits. With regard to symptoms, patients with ST-elevation ACS (STE-ACS) more frequently had associated symptoms and pain with an abrupt onset reaching maximum intensity within minutes. However, fewer than half the patients with STE-ACS had this type of symptom onset. There were more similarities than differences between genders and differences between age groups were minor (I). Three-quarters of the patients interpreted the symptoms as cardiac in origin. The majority contacted a family member after symptom onset, whereas few called directly for an ambulance. Approaching someone after symptom onset and the belief that the symptoms were cardiac in origin were factors associated with a shorter pre-hospital delay (II). Half the patients went to hospital by ambulance. Independent factors for ambulance use were knowledge of the importance of quickly seeking medical care and calling for an ambulance when experiencing chest pain, severe symptoms, abrupt onset of pain, STE-ACS, increasing age and distance to hospital of &gt; 5 km. Reasons for not calling for an ambulance were thinking self-transport would be faster or not being ill enough (III). Pain with abrupt onset, STE-ACS, symptoms such as vertigo or near syncope, experiencing the pain as frightening, interpreting the pain as cardiac in origin and knowledge were major factors associated with a short delay between symptom onset and decision to seek medical care, patient decision time (IV). The information campaign did not result in a reduction in patient decision time, but it appeared to increase ambulance use and the number of patients seeking the ED for acute chest pain (V).

One hundred haemorrhoid patients were compared with 300 matched control persons. Haemorrhoid symptoms and bowel symptoms were studied. Most common symptom of the patients was bleeding (44%), followed by prolapse (24%), hygiene problem (14%), pain (12%) and itching (5%). Bowel symptoms, as bloating and evacuation difficulties, possibly related to IBS, were frequent among the patients. 556 patients were operated upon with Milligan-Morgan haemorrhoidectomy. 418 (81%) answered a questionnaire on results, and on disturbances in anal continence. Totally140 (33%) reported recurrence, and 139 (33%) patients reported anal incontinence. Forty of the 139 patients associated this to the surgical procedure. Female gender was associated to increased risk of incontinence. The 40 patients who reported incontinence, were invited to undergo ano-rectal manometry, saline infusion test, endo-anal ultrasound, proctoscopy and clinical examination. Altogether 19 patients approved to participate. Matched control subjects and 15 persons previously operated for haemorrhoids, but without symptoms of incontinence, served as two reference groups. Incontinence score and saline infusion test showed significantly poorer continence in the patient group. Endo-anal ultrasound showed injury to the external sphincter in 20% of the patients. Anal pressure was slightly lower in the patient group, but the difference was not significant. Totally 225 patients were randomised to Milligan-Morgan or Ferguson haemorrhoidectomy. Primary aim was to study changes in anal continence. Other aims were to study postoperative pain, wound healing, complications, patient satisfaction and recurrence and changes in bowel function. Patients in the Ferguson group reported, slightly quicker wound healing (P=0.06). Postoperative pain was equal, as was rate of complications. After one year the Ferguson group reported lower incontinence score, and more satisfied patients. Recurrence rate was equal, 15-17%. Most bowel symptoms were reduced one year after surgery. In conclusion, functional bowel symptoms are common in haemorrhoid patients. Haemorrhoidectomy is associated with risk for incontinence in 5-10% of patients and females are at greater risk. A proportion of the patients who claim postoperative incontinence have physiological signs of sphincter incompetence, and external sphincter injuries are observed in those patients. Ferguson haemorrhoidectomy results in better anal continence and more satisfied patients.