Non-familial Type Research Articles

Giant solitary trichoepithelioma masquerading as basal cell carcinoma

Trichoepithelioma is a rare benign adnexal tumour which can be of solitary non-familial type or multiple familial trichoepitheliomas. Here authors describe a middle-aged patient who presented with a swelling of the left nasolabial region diagnosed clinically as a basal cell carcinoma but proved to be a giant solitary trichoepithelioma (GST) following histopathological examination. This case is presented due to the rarity and the difficulty encountered in diagnosis of the case.

Clinical and biochemical characteristics of familial type 1 diabetes mellitus (FT1DM) compared to non-familial type 1 DM (NFT1DM).

Familial type 1 diabetes mellitus (FT1DM) comprises parent-offspring and sib-pair subgroups. The clinical and genetic characteristics of FT1DM cases with and without affected family members have been previously studied with varying results. Some investigators found similarity of presenting features whereas others reported significant differences between the two groups. To describe the clinical and biochemical characteristics of children with FT1DM in comparison with those with non-familial type 1 diabetes mellitus (NFT1DM). We performed a cross-sectional retrospective study in a cohort of children and adolescents with T1DM (n=424) aged between 6 months - 16 years attending to Hamad General Hospital Pediatric Diabetes Center, Doha (Qatar) from 2012-2016. They were divided into 2 groups. Group 1 consisted of 62 children and adolescent with FT1DM (parent-offspring or sib-pair). The other group (Group 2) consisted of 431 children and adolescents with NFT1DM. The clinical presentation and prevalence of β-cell autoimmunity (anti-glutamic acid decarboxylase (GAD) antibodies , anti-islet cell and anti-insulin antibodies), thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibody (TPO) and anti-tissue transglutaminase (ATT) at their first presentation were recorded, described and analyzed. FT1 DM was more prevalent in boys versus girls (1.4:1, respectively) whereas the prevalence of NFT1DM did not differ between genders (1:1.1, respectively). F1DM occurred relatively early in childhood (40.7% before the age of 4 years and 72% before 9 years of age) versus NFT1DM which occurred relatively later in life (80% after the age of 4 years and 40% after the age of 9 years). 35.2% of FT1DM presented with diabetic ketoacidosis (DKA) versus 32.5% of T1DM patients. Anti-islet antibodies (Ab) were detected more frequently in FT1DM versus NFT1DM. The prevalence of positive anti-insulin and anti- GAD antibodies did not differ between the two groups. Anti TPO were detected in 27.2% of NFT1DM and 35.5% of FT1DM. A primary hypothyroidism, with positive ATPO, was more prevalent in FT1DM versus NFT1DM. ATT IgA was high in 5% of NFT1DM and 19.8% of FT1DM whereas ATT IgG was high in 4.4 % of NFT1DM and 15.4% of FT1DM. FT1DM is more prevalent in boys versus girls and occurs earlier in childhood compared to NFT1DM. Primary hypothyroidism was more prevalent in NFT1DM versus FT1DM. Anti-islet Ab and ATT antibodies were more prevalent in the FT1DM versus NFT1DM. The genetic background may explain some differences between FT1DM and NFT1DM including the age of onset, gender affection, as well as associated autoimmune disorders.

Xanthoma Disseminatum in a Young Patient with Diabetes Insipidus

Xanthoma disseminatum (XD) is a nonfamilial type of normolipidemic mucocutaneous xanthomatosis that belongs to the group of non-Langerhans cell histiocytoses. More than 100 cases of XD have been reported. In this study we report a case of XD in a 4-year-old boy with diabetes insipidus (DI). This boy is one of the youngest patients ever to present with XD combined with DI.

Nonfamilial Multiple Trichoepithelioma: Few and Far Between.

Trichoepithelioma is a rare benign adnexal tumor which may be of solitary nonfamilial type or multiple familial trichoepitheliomas. Here, we describe a rare presentation of nonfamilial case of trichoepithelioma in a 50-year-old female with multiple skin colored facial papules and nodules over the face, upper back, and extremities.

Non-syndromic and non-familial type of multiple basal cell carcinoma over unusual site.

We report a case of multiple basal cell carcinoma in a patient of albinism. which was non-familial, non-syndromic and having no history of chemical exposure. A 58 year old male with 4 lesions one over the left scapula (5*5 CM) for 4 years, over the right shoulder 3*2 CM for 3 and half years, over the right elbow 2*2CM and 1*2 CM for 3 years. Family history of basal cell carcinoma, xerodermapigmentosa and features of gorlin''s syndrome were absent, thats why, this is a rare case of multiple basal cell carcinoma which occurred in absence of familial, and various chemical exposure mentioned in standard literature

Persistent thrombocytosis in elderly patients with rare hyposplenias that mimic essential thrombocythemia

When elderly patients present with persistent thrombocytosis, myeloproliferative disease, iron-deficiency anemia or post-splenectomy status are suspected along with autoimmune diseases. Reported here are the cases of two elderly patients with persistent thrombocytosis due to hyposplenia, which is very rarely diagnosed in old age. Case 1 was a 72-year-old man whose thrombocytosis was due to non-familial type isolated congenital asplenia. Case 2 was a 74-year-old man whose thrombocytosis was caused by an atrophied spleen resulting from perforated stomach ulcer-related panperitonitis that had been treated 20 years previously. Both patients had thrombocyte counts exceeding >500,000/μl in association with small vestigial spleen tissue on a computed tomography scan and positive Howell-Jolly bodies on the blood smear. A correct diagnosis is essential for the management of persistent thrombocytosis.

TNM staging and classification (familial and nonfamilial) of breast cancer in Jordanian females

Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS) cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

Chromosome banding pattern in human colonic polyps.

The chromosome pattern was studied by conventional and Giemsa banding techniques in 5 polyps from one patient with polyposis coli and in sporadic adenomas from 4 patients. In both the familial and the non-familial types chromosomal changes preceded histologic signs of invasiveness. In both types preferential engagement of chromosomes Nos. 8 and 14 was found, suggesting a similar chromosomal evolution in colonic adenomas regardless of whether they have a hereditary basis or not. The rate of progression, however, was faster in the familia type of colonic polyps, which may reflect the more malignant potential of these tumors.

Congenital Bilateral Perisylvian Syndrome: Familial Occurrence, Clinical and Psycholinguistic Aspects Correlated with MRI

Congenital bilateral perisylvian syndrome (CBPS) is frequently caused by polymicrogyria (PMG). The aim of this study was to correlate the clinical and psycholinguistic aspects with neuroradiological data of patients with CBPS. Thirty-one patients were studied. We performed a clinical investigation of the patients and their families, including MRI scanning, neuropsychological tests and language evaluation. The statistical analysis showed that: a) prenatal events are associated with the non-familial type of PMG; b) diffuse PMG is associated with pseudobulbar signs, as opposed to BPPP; c) motor deficit is associated with diffuse PMG; d) epilepsy is equally present in patients with both familial or non-familial PMG, but is more frequently seen in patients with diffuse PMG; e) dyslexia and SLI can be a feature of both the diffuse or BPPP, and either familial or sporadic cases of PMG. The severity of clinical manifestations in CBPS is correlated with the extent of cortical involvement. Most patients with CBPS have a history of speech delay or language difficulties and no epilepsy. Dyslexia can be found in patients with PMG.

Newborns at risk for special education placement: A population-based study

Objectives To establish the contributions of birth weight (BW), gender, socioeconomic status (SES), and parental age on risks for special education (SE) placements in school-age children. Methods A population-based sample of 900 school-age children attending the following full-time SE groups: at level 1, children had isolated neurodevelopmental, physical, or other impairments; at level 2, borderline to mild intellectual disability (ID); and at level 3, moderate to severe ID. Three hundred and one children enrolled in mainstream education formed the control group (level 0). For all children with siblings, we defined familiar forms of learning disorders as having a sibling in one of the SE groupings. We performed our analysis for the entire cohort as well as comparing risk factors within the familial and non-familial types of SE groupings. Results In multinomial logistic regression analysis, age of father ⩾40 years, low BW (<2500 g or <−2 SD), male sex, and parent's lower SES, all increased the probability of SE placement. In the familial forms of levels 2 and 3, the parental SES was lower and, in addition, in the level 2, the family size was bigger. Furthermore, in the non-familial form of level 2, both the low and the high (⩾4000 g) BW were more common. Conclusions Among the known risk factors for learning disabilities (LD), our study highlighted the importance of a higher paternal age and a lower SES especially in the familial forms of LD.

Combination of NADPH and Copper Ions Generates Proteinase K-resistant Aggregates from Recombinant Prion Protein

Recent studies have demonstrated that the octapeptide repeats of the N-terminal region of prion protein may be responsible for de novo generation of infectious prions in the absence of template. Here we demonstrate that PrP-(23-98), an N-terminal portion of PrP, is converted to aggregates upon incubation with NADPH and copper ions. Other pyridine nucleotides possessing a phosphate group on the adenine-linked ribose moiety (the reduced form of nicotinamide adenine dinucleotide 3'-phosphate, nicotinic acid adenine dinucleotide phosphate, and NADP) were also effective in promoting aggregation, but NADH and NAD had no effect. The aggregation was attenuated by the metal chelator EDTA or by modification of histidyl residues with diethyl pyrocarbonate. The aggregates are amyloid-like as judged by the binding of thioflavin T, a fluorescent probe for amyloid, but do not exhibit fibrillar structures according to electron micrography. Interestingly the aggregates were resistant to proteinase K digestion. Likewise NADPH and zinc ions caused aggregation of PrP-(23-98), but the resulting aggregates were susceptible to degradation by proteinase K. Upon incubation with NADPH and copper ions, the full-length molecule PrP-(23-231) also formed proteinase K-resistant amyloid-like aggregates. Because it is possible that PrP, NADPH, and copper ions could associate in certain tissues, the aggregation observed in this study may be involved in prion initiation especially in the nonfamilial types of prion diseases.

Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis.

The congenital dyserythropoietic anemias (CDAs) comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by distinct morphological abnormalities of the majority of erythroblasts in the bone marrow. The classification in three types as proposed in 1968 is still valid, but there is genetic heterogeneity within each type, and there are additional variants of unknown genetic basis. CDA II is the most frequent, and the nonfamilial type of CDA III the rarest group. The genes of CDA II and CDA III were mapped to chromosome 20 and 15, respectively, and the gene of CDA I on 15q was recently cloned. Therapeutic decision making requires definition of the type, an estimate of individual severity, and presence of or risk for complications. Therapeutic measures include interferon-alpha for CDA I, splenectomy for CDA II, and iron depletion for all individuals at risk for secondary hemochromatosis.

Frontotemporal degenerative dementias

Frontotemporal dementia (FTD) is a clinical term now used for a group of dementing neurodegenerative disorders marked clinically by general predominance of symptoms referable to the frontal lobes. Symptoms may include changes in language ability with expressive or receptive aphasia, and changes in personality, including disinhibited, obsessive, hyperoral, hypersexual, repetitive, and perseverative behaviors. Memory is often affected, but is usually not a primary symptom. Characteristically, analytic, navigational, and other visuospatial abilities may be quite preserved. The clinical symptomatology of FTD contrasts with the general predominance of temporal and parietal symptoms in the most common neurodegenerative disorder, Alzheimer's disease (AD). FTD symptoms also differ from those seen with the second most common neurodegenerative disorder, Lewy Body Dementia (LBD), which while having substantial clinical and pathological overlap with AD, often shows additional clinical visuospatial (occipital) and parkinsonian symptomatology. FTD likely constitutes the third most-common cause of degenerative dementia. Clinical overlap can sometimes make it difficult to distinguish individual cases from AD. Genetic studies have shown that FTD, like AD, occurs in both familial and nonfamilial types, and a proportion of FTD cases arise from autosomal dominant genetic disorders due to mutations in the tau gene. Some recent formulations include in the family of frontal degenerative disorders other dementias with frontal symptomatology such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Lending support to such a grouping, neuropathological studies show a group of histologies, sometimes including PSP and CBD, to be the substrates for clinical FTD.

Frontotemporal degenerative dementias

Frontotemporal dementia (FTD) is a clinical term now used for a group of dementing neurodegenerative disorders marked clinically by general predominance of symptoms referable to the frontal lobes. Symptoms may include changes in language ability with expressive or receptive aphasia, and changes in personality, including disinhibited, obsessive, hyperoral, hypersexual, repetitive, and perseverative behaviors. Memory is often affected, but is usually not a primary symptom. Characteristically, analytic, navigational, and other visuospatial abilities may be quite preserved. The clinical symptomatology of FTD contrasts with the general predominance of temporal and parietal symptoms in the most common neurodegenerative disorder, Alzheimer's disease (AD). FTD symptoms also differ from those seen with the second most common neurodegenerative disorder, Lewy Body Dementia (LBD), which while having substantial clinical and pathological overlap with AD, often shows additional clinical visuospatial (occipital) and parkinsonian symptomatology. FTD likely constitutes the third most-common cause of degenerative dementia. Clinical overlap can sometimes make it difficult to distinguish individual cases from AD. Genetic studies have shown that FTD, like AD, occurs in both familial and nonfamilial types, and a proportion of FTD cases arise from autosomal dominant genetic disorders due to mutations in the tau gene. Some recent formulations include in the family of frontal degenerative disorders other dementias with frontal symptomatology such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Lending support to such a grouping, neuropathological studies show a group of histologies, sometimes including PSP and CBD, to be the substrates for clinical FTD.

Effects of Fluvastatin on Plasma Levels of Low-Density Lipoprotein Subfractions, Oxidized Low-Density Lipoprotein, and Soluble Adhesion Molecules: A Twenty-Four–Week, Open-Label, Dose-Increasing Study

Background: Statins not only lower low-density lipoprotein (LDL) levels, but also have several antiarteriosclerotic effects (eg, decreasing arterial inflammation and arterial smooth muscle cell proliferation, as well as antioxidant effects). The relationship between the dose of statin and its effects on plasma LDL levels and other arteriosclerosis-related effects remains to be clarified. Objective: We investigated the effect of a statin, fluvastatin, on plasma levels of lipoprotein subfractions, oxidized LDL (Ox-LDL), Ox-LDL immunoglobulin G (IgG), soluble adhesion molecules, reverse cholesterol transport (ie, transport of esterified high-density lipoprotein cholesterol [HDL-C] to triglyceride [TG]-rich lipoproteins by cholesteryl ester transfer protein [CETP] and reduction of plasma HDL-C levels), and on the intima-medial thickness (IMT) of the common carotid arteries. Methods: Patients with nonfamilial type 2 hyperlipoproteinemia were eligible for this open-label, dose-increasing study. Fluvastatin 20 mg/d was administered for the first 12 weeks, and the daily dose was increased to 40 mg for the subsequent 12 weeks. Patients were examined at baseline and after 12 and 24 weeks of treatment. Plasma lipoprotein subfractions were determined using sequential ultracentrifugation at 100,000 g. The plasma levels of Ox-LDL, Ox-LDL-IgG, CETP, and soluble adhesion molecules were measured using sandwich enzyme-linked immunosorbent assay. The maximum IMT of the common carotid arteries was measured using sonography. Results: The plasma levels of LDL cholesterol (LDL-C) and apolipoprotein (apo) B were reduced by 25% and 17%, respectively ( P<0.001 for both), after 12 weeks of treatment with fluvastatin 20 mg/d; no further significant reductions in LDL were observed after increasing the daily dose to 40 mg. Fluvastatin 20 mg/d for 12 weeks decreased plasma levels of intermediate-density lipoprotein cholesterol, LDL-I-C, LDL-II-C, and LDL-III-C by 25% ( P<0.01), 30% ( P<0.001), 23% ( P<0.01), and 20% ( P = 0.02), respectively. No further significant reductions in these levels were observed after increasing the daily dose to 40 mg. The plasma levels of Ox-LDL decreased in a similar fashion to the plasma levels of LDL-C ( P<0.001). However, plasma levels of Ox-LDL-IgG and soluble P-selectin did not decrease after 12 weeks of fluvastatin 20 mg/d, but did decrease significantly (both 22%) after the next 12 weeks of treatment with fluvastatin 40 mg/d ( P<0.05). Plasma levels of intercellular adhesion molecule 1and vascular cell adhesion molecule 1 and CETP mass were not altered by fluvastatin treatment. Significant changes in maximum IMT of the common carotid arteries were not seen throughout 24 weeks of fluvastatin treatment. Conclusions: In this patient population, fluvastatin 20 mg/d was sufficient to significantly reduce plasma levels of LDL, the 3 LDL subfractions, and Ox-LDL, but was not sufficient to reduce plasma levels of Ox-LDL-IgG and soluble P-selectin. It is important to check not only plasma lipoprotein levels but also other factors relating to arteriosclerosis during treatment with statins for the prevention and treatment of arteriosclerosis.

Mutations in RNA: a f irst example of molecular misreading in Alzheimer's disease

In the past decade, considerable progress has been made in the understanding of the neurodegenerative changes that occur in Alzheimer's disease (AD). Knowledge about this disease is based mainly on studies of inherited forms of AD, although most cases of AD are of the non-familial type. Recently, a novel type of mutation in `vulnerable' dinucleotide repeats in messenger RNA was discovered in AD patients: in this type of mutation a mutated transcript is produced from a correct DNA sequence, a process that we call `molecular misreading'. The resulting mutated `+1 proteins' are prominent neuropathological hallmarks of AD and they are present in most elderly non-demented people also. This suggests that the dinucleotide deletions in transcripts could be one of the earliest events in the neuropathogenesis of AD and an important factor in normal aging.

Effects of simvastatin on plasma lipoprotein subfractions, cholesterol esterification rate, and cholesteryl ester transfer protein in type II hyperlipoproteinemia

We investigated the effects of simvastatin on plasma levels of lipoprotein subfractions, cholesterol esterification rates and activities of cholesteryl ester transfer protein in 28 patients with type II hyperlipoproteinemia (i.e., nonfamilial hyperlipoproteinemia type IIa and type IIb, and heterozygous familial hypercholesterolemia (FH)). Plasma levels of VLDL-cholesterol (C) and VLDL-triglyceride (TG) were significantly reduced overall by 12.9 ± 58.0% (mean ± S.D.; P < 0.05) and 4.2 ± 54.2% ( P < 0.05) respectively, but not in FH. Plasma levels of IDL-C and IDLT-G were decreased overall by 23.2 ± 47.5% ( P < 0.001) and 12.3 ± 49.7% ( P < 0.05), respectively, again mainly due to decreases seen in nonfamilial type II hyperlipoproteinemia. Plasma levels of LDL1 (1.019 < d < 1.045)-C and LDL1-TG were significantly reduced by 33.1 ± 12.9% ( P < 0.001) and 23.3 ± 24.7% ( P < 0.001), respectively. Plasma levels of LDL2 (1.045 < d < 1.063)-C were significantly reduced by 22.9 ± 18.1% ( P < 0.001) overall but not in FH. Gradient PAGE showed no consistant changes in the distribution of LDL particles. Thus, plasma levels of all apo B-containing lipoprotein subfractions were reduced by simvastatin, but its effects varied among the three subgroups. Cholesterol esterification rates were suppressed by 9.3 ± 19.7% ( P < 0.01) and activities of cholesteryl ester transfer protein were reduced by 30.6 ± 21.5% ( P < 0.001). Changes in CETP activity and in plasma levels of cholesterol in lipoprotein subfractions were not correlated. Thus, the changes in distribution of lipoprotein subfractions were not due mainly to CETP suppression.

Mass screening to identify babies with dyslipoproteinemia by measuring the levels of apoA-I, apoB and the ratio of apoB to apoA-I on dried blood spots

We screened 18-month-old babies with dyslipoproteinemia by measuring the levels of apolipoprotein (apo) A-I, apoB and the ratio of apoB to apoA-I on a dried blood spot (DBS). We used simple and efficient radial immunodiffusion assays for apoA-I and apoB on DBS. ApoA-I on DBS closely correlated with plasma apoA-I ( r=0.96, n=107). ApoB levels on DBS also correlated well with plasma apoB ( r=0.90, n=107). The elutions of apoA-I and apoB from DBS were stable for up to 7 days and 14 days, at room temperature, respectively. DBS were obtained by ear-prick from 18-month-old babies at public health-care centers. The values were arbitrarily considered abnormal when the apoB and apoB/apoA-I levels were more than + 2.5 SD above the mean, and the apoA-I level was less than - 2.5 SD under the mean. Values were abnormal in I85 babies; of those we reinvestigated 159 babies (86%). Among them, II babies were diagnosed as cases of familial hypercholesterolemia, through the family studies. Others were non-familial type Ha (54 infants), type IIb (3) and type IV (12) hyperlipidemic and hypoalphalipoproteinemic (58) subjects. The remaining 2I babies (13%) had normal plasma lipid and apolipoprotein levels. This screening is useful for detecting dyslipoproteinemic babies.

Inhibition of cholesterol biosynthesis in freshly isolated blood mononuclear cells from normolipidemic subjects and hypercholesterolemic patients treated with bezafibrate

Bezafibrate was given for 15 days at a dose of 200 mg t.i.d. to 4 normolipidemic subjects, to 5 patients with putative heterozygous familial hypercholesterolemia, and to 6 patients with primary hypercholesterolemia of the non-familial type. At the end of the treatment, the rate of incorporation of labelled acetate into non-saponifiable lipids in freshly isolated blood mononuclear cells decreased in all subjects. On the average, acetate incorporation decreased by 31% in cells from normolipidemic subjects, 41% in cells from familial, and 45% in cells from non-familial hypercholesterolemia patients. Results of the present study suggest that the lowering effect of bezafibrate on serum cholesterol is mainly due to the inhibition of cholesterol synthesis through the suppression of HMG-CoA reductase as was demonstrated in rat hepatocytes and in cultured human blood mononuclear cells.

非家族性高コレステローノレ血症におけるプラバスタチンのリポ蛋白, アポ蛋白に対する効果

Plasma lipids, lipoproteins and apolipoproteins (apo) were measured in 17 patients with nonfamilial type II hyperlipoproteinemia over a 12-month period during treatment with pravastatin (10-30mg twice daily). The patients were divided into two groups: type ha (n=7) and type IIb (n=10). Type IIb patients had lower high density lipoprotein (HDL)-cholesterol levels and greater very low density lipoprotein-triglyceride (VLDL-TG) levels at the beginning of the study period. There were, however, no significant differences in total plasma cholesterol and low density lipoprotein (LDL)-cholesterol levels between the two groups.Pravastatin induced a decrease in total cholesterol from 288±12 to 233±11mg/dl and in LDL-cholesterol from 191±11 to 138±9mg/dl 3 months after initiating drug therapy. Reductions in plasma cholesterol of 20% and in LDL-cholesterol of 30% were maintained throughout the study. Pravastatin also produced a decrease in apo B from 151±8 to 137±10mg/dl at 3 months, followed by a further decrease to 110±6mg/dl at the end of the study. These responses to pravastatin were almost the same in both groups.In contrast, the two types showed different plasma TG and HDL-cholesterol responses to pravastatin. In type ha patients, there was no significant change in TG in the plasma, VLDL, and HDL-cholesterol levels in response to pravastatin. In type IIb patients, pravastatin produced a 20%-decrease in plasma TG after 3 and 12 months, although a larger decrease of 40 % was found at 9 months. These changes were mainly due to decreases in VLDL-TG levels and were associated with reductions in apo C-II and C-III. In addition, a small but significant increase in HDL-cholesterol was found at 12 months in type IIb patients, although there was no significant change from 3 through 9 months after pravastatin administration. These changes paralleled changes in apo A-I and A-II.The ratio of LDL-cholesterol to HDL-cholesterol, therefore, decreased from 3.64±0.30 to 2.35±0.19 at 3 months and to 2.36±0.16 at 12 months. Pravastatin was well tolerated in all patients and produced no abnormalities in serum chemistry screening and urine analysis. This study demonstrates that pravastatin is useful in lowering plasma LDL-cholesterol without reducing HDL-cholesterol in nonfamilial type II hyperlipoproteinemia.